Abstract
Stimulus-coupled incretin secretion from enteroendocrine cells plays a fundamental role in glucose homeostasis and could be targeted for the treatment of type 2 diabetes. Here, we investigated the expression and function of transient receptor potential (TRP) ion channels in enteroendocrine L cells producing GLP-1. By microarray and quantitative PCR analysis, we identified trpa1 as an L cell-enriched transcript in the small intestine. Calcium imaging of primary L cells and the model cell line GLUTag revealed responses triggered by the TRPA1 agonists allyl-isothiocyanate (mustard oil), carvacrol, and polyunsaturated fatty acids, which were blocked by TRPA1 antagonists. Electrophysiology in GLUTag cells showed that carvacrol induced a current with characteristics typical of TRPA1 and triggered the firing of action potentials. TRPA1 activation caused an increase in GLP-1 secretion from primary murine intestinal cultures and GLUTag cells, an effect that was abolished in cultures from trpa1(-/-) mice or by pharmacological TRPA1 inhibition. These findings present TRPA1 as a novel sensory mechanism in enteroendocrine L cells, coupled to the facilitation of GLP-1 release, which may be exploitable as a target for treating diabetes.
Original language | English |
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Pages (from-to) | 1202-10 |
Number of pages | 9 |
Journal | Diabetes |
Volume | 64 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 2015 |
Keywords
- Animals
- Calcium
- Cells, Cultured
- Enteroendocrine Cells
- Glucagon-Like Peptide 1
- Intestine, Small
- Mice
- Mice, Knockout
- Signal Transduction
- Transient Receptor Potential Channels